classification of drugs used in depression
- MAOIs
- TCAs
- SSRIs
- SNRIs (serotonin and norepi reuptake inhibitors)
- NaSSA (noradrenergic & specific serotonergic antidepressants)
- 5HT2 blockers that are also reuptake inhibitors
- NDRIs (norepi and dopamine reuptake inhibitors)
- multimodal antidepressants
- mood stabilizers
(1-8 are specific classes of antidepressants; in order of introduction to market)
name the MAOIs
- phenelzine (Nardil)
- tranylcypromine (Parnate)
- isocarboxazid (Marplan)
- selegiline (Deprenyl, Eldepryl)
- Emsam patch which is mostly used for Parkinson disease and depression
Info about MAOIs
MOA: inhibit enzyme MAO so NE/5HT not degraded; adrenergic, serotonergic
AEs: orthostatic hypotension, insomnia, sexual dysfunction, dietary issues (tyramine can cause hypertensive crisis);
Drug-drug: numerous/severe; 1. stimulants (cocaine, diet pills, nasal decongestants)
- narcotic analgesics (meperidine, Demerol)
- SSRIs/TCAs - wait min 2 weeks when switching from/to these med, otherwise causes serotonin syndrome - leads to fatal hypertensive crisis + GI problems
Other: first AD, only for non-responsive patients
Food rich in tyramine
cheese especially aged (philly cream cheese and cottage cheese exceptions), chicken/beef liver, yeast preparations (baker’s yeast ok), fava/broad beans, herring, beer, sherry, red wine, ale, liquers, canned figs, proteins extracts, bologna, salami, pepperoni, Spam
(excessive use to avoid, yogurt, sour cream, ripe acovados/guac, choco, caffeine, white wine, liquors)
name the TCAs
- amitriptyline (Elavil)
- nortriptyline (Pamelor)
- protriptyline (Vivactil)
- imipramine (Tofranil)
- clomipramine (Anafranil)
- desipramine (Norpramin)
- trimipramine (Surmontil)
- amoxapine (Asendin)
- doxepin (Sinequan)
- maprotiline (Ludiomil)
Info on TCAs
MOA: increases 5HT/NE in brain; adrenergic/serotonergic
AEs: antihistamine aes of weight gain/drowsiness, anticholinergic of can’t see (worsened glaucoma)/spit/pee/shit, drowsiness; confusion, orthostatic hypotension
- > amoxapine: TD
- > aprotline/clomipramine: seizures
- > really bad for geriatric patients
overdose: especially toxic to children, cardiac effects
usefulness: off-label pain management, older ADs mainly for non-responsive patients
Name the SSRIs
- paroxetine (Paxil/CR, Pexeva)
- sertraline (Zoloft)
- fluoxetine (Prozac, Sarafem)
- fluvoxamine (Luvox)
- citalopram (Celexa)
- escitalopram (Lexapro) - related S-enantiomer drug
Info on SSRIs
most commonly used AD class today b/c of improved safety
MOA: block 5HT reuptake in synapse (purely serotonergic)
Usefulness: all label indicated for MDD
off-label: pruritus, smoking cessation, chronic pain, menopausal vasomotor instability/hotflushes, premature ejaculation
ANXIETY SYNDROMES
1. paroxetine: GAD, panic disorder, OCD, social anxiety disorder, PTSD
2. sertraline: panic, OCD, social anxiety, PTSD
3. escitalopram: GAD, OCD
4. fluoxetine: panic, OCD
5. fluvoxamine: social anxiety, OCD
AEs: panicogenic (may cause panic attacks though used to treat panic disorders, called paradoxical reaction), sexual dysfunction, nausea/diarrhea due to 5HT effect in GI tract, risk of bleeding due to platelet effects, headache, bruxism, hyponatremia, discontinuation syndrome, serotonin syndrome with serotonergic drugs, some teratogenic - pulmonary disease in infants born to mothers on SSRIs
drug-drug: sometimes results in cardiac problems (long QT syndrome), sometimes reduced effectiveness of other drugs, never use within two weeks of MAOI, with lithium may enhance serotonergic effects
Name the SNRIs
- venlafaxine (Effexor-XR/immediate release)
- desvenlafaxine (Pristiq), the active component of venlafaxine
- duloxetine (Cymbalta)
- levomilnacipran (Fetzima)
Info of SNRIs
MOA: increases 5HT and NE in brain (adrenergic/serotonergic), at higher doses may increase dopamine in brain
AEs: since serotonergix, all AEs of SSRIs
venlafaxine - HTN
duloxetine - hepatitis, jaundice
Usefulness
label and off-label: 1. MDD and relapse prevention
2. GAD, PTSD, social anxiety, panic
3. fibromyalgia, diabetic peripheral neuropathy (DPN)
note: milnacipran (Savella) is also an SNRI used to treated fibromyalgia ONLY, thus it’s not listed in depression meds
drug-drug: duloxetine interacts with quinolone antibiotics
so summary of specifics: diastolic HTN, hyponatremia (low blood sodium), hepatitis/jaundice with duloxetine
Name the NaSSA drugs
- mirtazapine (Remeron and Remeron SolTab dissolving tablet)
Info on NaSSA drugs
really here for mirtazapine
MOA: raises levels of NE/5HT by receptor blockade in brain
AEs: antihistamine properties of weight gain, sedation, drowsiness, and dizziness (anticholinergic of dry mouth); risk of elevated cholesterol/triglycerides; risk of neutropenia (agranulocytosis)
drug-drug: with MAOIs; portentiates alcohol, benzos, CNS sedatives, and some anti-HTNs
Name the 5HT2 blockers that are also reuptake inhibitors
- trazadone (Desyrel)
2. nefazodone (Serzone)
infor on 5HT2 blockers that are also reuptake inhibitors
MOA: serotonergic effects from blockade of 5HT2 receptor
Usefulness: MDD (depression), reduces anxiety, sedation to treat insomnia
AEs: priapism, seizures, drowsiness, leucopenia, elevated LFTs (liver function tests)
nefazodone (Serzone): black box of liver failure
drug-drugs: other sedatives; MAOIs
special:
trazodone: prob safest AD if patient takes an overdose, often used at bedtime for insomnia, add-on to SSRIs often to reverse ED and libido loss
are all 5HT2 blockers antidepressants?
no, though others have similar sedation effects
- antihistamine: cyproheptadine (Periactin) used in migraine prophylaxis in children and used to for anorexia in children/adolescents
- migraine prophylaxis drug: methysergide (potential for severe toxicity)
- atypical antipsychotics: risperidone (Risperdal); olanzapine (Zyprexa)
what are the NDRIs
- bupropion (Wellbutrin/SR/XL and Zyban which is label-indicated for smoking cessation)
info on NDRIs
MOA: adrenergic/dopaminergic by reuptake inhibition; **ONLY drug class that is dopaminergic aka not usually sexual dysfunction
Usefulness: MDD, SAD
AEs: immediate release form - seizure acitivity in epileptic patients
- for all, seizure activity/risk contraindicated
Benefits: less sedating, rarely sexual dysfunction, preg cat C and possibly best AD for pregnant women, sometimes add-on for SSRI-induced sexual dysfunction (like trazodone), smoking cessation help
Drawbacks: no anxiety benefit so no use for bulimia/anorexianervosa, mania/psychosis, or other anxiety symptoms
Name the multimodal antidepressants
called this b/c multiple actions on receptors/uptake pumps
- DUAL SSRI + 5-HT1A receptor partial agonist vilazadone (Viibryd)
- SSRI + 5-HT3 receptor antagonist + 5HT1A agonist: vortioxetine (Brintellix)
info on multimodal antidepressants
- vilazadone (Viibryd)
pharm profile: serotonin antagonist at 5HT1A, SSRI effect
NOTE: supposed to be less/no sexual side effects as seen with pure SSRI drugs; NOT approved for pediatric use
Dose: 10,20,40mg tabs available
2) vortioxetine (Brintellix)
pharm profile: SSRI, 5-HT3 antagonist, 5-HT1A agonist
note: less/nosexual side effects as pure SSRIs, not pediatric use, may cause more nausea than other serotonergic agents, metabolized by CYP2D6 (inhibitor of this enzyme will raise vortioxetine levels like amiodarone, doxorubicin, ritonavir, valproate, yohimbine)
drug-drug interactions for ALL serotonergic drugs
- caution with alcohol/CNS depressants
- serotonin syndrome - don’t mix with other serotonergic drugs like SSRIs, St. John’s wort, triptans, ergotamines, tramadol (Ultram), lithium
- NEVER use within 2 weeks of MAOIs
- all SSRIs interact with tryptophan (severe GI)
- cholinergic drugs for dementia (tacrine, donezepril, rivastigmine) = severe GI effects
What are the mood stabilizer used in depression
- Thyroid drug: Cytomel (T3) (tri-iodothyroxine) - must adjust dose of T4 if taking thyroxine, start 12.5 Cytomel mg daily and raise to 25 mg if works – monitor for AEs of excessive thyroid admin
- AEDs: carbamazepine (Tegretol), gabapentin (Neurontin), clonazepam (Klonopin), valproate (Depakote)
- CNS stimulants like methylphenidate
- non-stimulant wakefulness promoters like modafinil (Provigil)
- non-ergot dopamine agonists (normally used in parkinson’s disease) like pramipexole (Mirapex)
- Omega-3 fatty acids (Lovaza): 2-9 gm/day risk of bleeding over 4gm/day
what is CAM and what are the CAM drugs for depression
CAM: complementary and alternative medicine in depression; non-FDA approved
- St. John’s wort (hypericum, hypericin)
- SAMe (s-adenosyl-methionine, SAM, ademetionine)
Info on CAM for depression
- St. John’s wort
notes: active ingredient is hypericin from above-groun part of plant (just before flowering); SSRI-like effects (serotonergic agent)
AEs: cataract development (UV rays-wear sunglasses) and photosensitivity
Drug-drug: serotonin syndrome with other serotonergics
- CYP3A4 interaction: may reduce other drugs such as…..
a. cyclosporine resulting in organ graft rejection
b. oral contraceptive efficacy w/ bleeding and escape ovulation - preg risk
c. protease inhibitor (PI) failure and non-nucleoside reverse transcriptase inhibitor (NNRTI) failure - treatment failure and HIV resistance or AIDs
d. theophylline/warfarin levels reduced, digoxin increased
SAMe (s-adeonsyl-methionine, SAM, ademetionine)
- serotonergic/adrenergic
- used in depression by herbalists
- not much known about it potential for toxicity
drugs used in treating PMS/PMDD
- SSRIs: fluoxetine (Sarafem), sertraline (Zoloft), paroxetine (Paxil)
- OCs: Yaz (low-dose estrogen plus drospirenone)
